PAK1 and Therapy Resistance in Melanoma
Malignant melanoma claims more lives than any other skin malignancy. While primary melanomas are usually cured via surgical excision, the metastatic form of the disease portents a poor prognosis. Decades of intense research has yielded an extensive armamentarium of anti-melanoma therapies, ranging f...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/19/2373 |
| _version_ | 1827722691045490688 |
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| author | Julia V. Kichina Alexei Maslov Eugene S. Kandel |
| author_facet | Julia V. Kichina Alexei Maslov Eugene S. Kandel |
| author_sort | Julia V. Kichina |
| collection | DOAJ |
| description | Malignant melanoma claims more lives than any other skin malignancy. While primary melanomas are usually cured via surgical excision, the metastatic form of the disease portents a poor prognosis. Decades of intense research has yielded an extensive armamentarium of anti-melanoma therapies, ranging from genotoxic chemo- and radiotherapies to targeted interventions in specific signaling pathways and immune functions. Unfortunately, even the most up-to-date embodiments of these therapies are not curative for the majority of metastatic melanoma patients, and the need to improve their efficacy is widely recognized. Here, we review the reports that implicate p21-regulated kinase 1 (PAK1) and PAK1-related pathways in the response of melanoma to various therapeutic modalities. Ample data suggest that PAK1 may decrease cell sensitivity to programmed cell death, provide additional stimulation to growth-promoting molecular pathways, and contribute to the creation of an immunosuppressive tumor microenvironment. Accordingly, there is mounting evidence that the concomitant inhibition of PAK1 enhances the potency of various anti-melanoma regimens. Overall, the available information suggests that a safe and effective inhibition of PAK1-dependent molecular processes would enhance the potency of the currently available anti-melanoma treatments, although considerable challenges in implementing such strategies still exist. |
| first_indexed | 2024-03-10T21:47:32Z |
| format | Article |
| id | doaj.art-5660dac1d4d640f691a6ebc8d0a772d5 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T21:47:32Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-5660dac1d4d640f691a6ebc8d0a772d52023-11-19T14:12:52ZengMDPI AGCells2073-44092023-09-011219237310.3390/cells12192373PAK1 and Therapy Resistance in MelanomaJulia V. Kichina0Alexei Maslov1Eugene S. Kandel2Department of Immunology, Roswell Park Comprehensive Cancer Center, Elm & Carlton St., Buffalo, NY 14263, USADepartment of Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Elm & Carlton St., Buffalo, NY 14263, USADepartment of Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Elm & Carlton St., Buffalo, NY 14263, USAMalignant melanoma claims more lives than any other skin malignancy. While primary melanomas are usually cured via surgical excision, the metastatic form of the disease portents a poor prognosis. Decades of intense research has yielded an extensive armamentarium of anti-melanoma therapies, ranging from genotoxic chemo- and radiotherapies to targeted interventions in specific signaling pathways and immune functions. Unfortunately, even the most up-to-date embodiments of these therapies are not curative for the majority of metastatic melanoma patients, and the need to improve their efficacy is widely recognized. Here, we review the reports that implicate p21-regulated kinase 1 (PAK1) and PAK1-related pathways in the response of melanoma to various therapeutic modalities. Ample data suggest that PAK1 may decrease cell sensitivity to programmed cell death, provide additional stimulation to growth-promoting molecular pathways, and contribute to the creation of an immunosuppressive tumor microenvironment. Accordingly, there is mounting evidence that the concomitant inhibition of PAK1 enhances the potency of various anti-melanoma regimens. Overall, the available information suggests that a safe and effective inhibition of PAK1-dependent molecular processes would enhance the potency of the currently available anti-melanoma treatments, although considerable challenges in implementing such strategies still exist.https://www.mdpi.com/2073-4409/12/19/2373chemotherapyimmune therapytargeted therapycutaneous melanomaacral melanomauveal melanoma |
| spellingShingle | Julia V. Kichina Alexei Maslov Eugene S. Kandel PAK1 and Therapy Resistance in Melanoma Cells chemotherapy immune therapy targeted therapy cutaneous melanoma acral melanoma uveal melanoma |
| title | PAK1 and Therapy Resistance in Melanoma |
| title_full | PAK1 and Therapy Resistance in Melanoma |
| title_fullStr | PAK1 and Therapy Resistance in Melanoma |
| title_full_unstemmed | PAK1 and Therapy Resistance in Melanoma |
| title_short | PAK1 and Therapy Resistance in Melanoma |
| title_sort | pak1 and therapy resistance in melanoma |
| topic | chemotherapy immune therapy targeted therapy cutaneous melanoma acral melanoma uveal melanoma |
| url | https://www.mdpi.com/2073-4409/12/19/2373 |
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